1. Criteria for internal validity.

Criteria

Was the method of randomization adequate? A random (unpredictable) assignment sequence. Was the treatment allocation concealed? Assignment generated by an independent person not responsible for determining the eligibility of the patients. This person has no information about the persons included in the trial and has no influence on the assignment sequence or on the decision about eligibility of the patient. Was the patient blinded to the intervention? The reviewer determines if enough information about the blinding is given in order to score a "yes." Was the care provider blinded to the intervention? The reviewer determines if enough information about the blinding is given in order to score a "yes." Was the outcome assessor blinded to the intervention? The reviewer determines if enough information about the blinding is given in order to score a "yes." Was the drop‐out rate described and acceptable? The number of participants who were included in the study but did not complete the observation period or were not included in the analysis must be described and reasons given. If the percentage of withdrawals and drop‐outs does not exceed 20% for short‐term follow‐up and 30% for long‐term follow‐up and does not lead to substantial bias a "yes" is scored. Did the analysis include an intention‐to‐treat analysis? All randomized patients are reported/analyzed in the group they were allocated to by randomization for the most important moments of effect measurement (minus missing values) irrespective of noncompliance and co‐interventions. Were the groups similar at baseline regarding the most important prognostic indicators? In order to receive a "yes", groups have to be similar at baseline characteristics. Were co‐interventions avoided or similar? Co‐interventions should either be avoided in the trial design or similar between the index and control groups. Was the compliance acceptable in all groups? The reviewer determines if the compliance to the interventions is acceptable. Was the timing of the outcome assessment in all groups similar? Timing of outcome assessment should be identical for all intervention groups and for all important outcome assessments.